Acute and recurrent virus induced nervous system diseases, chronic degenerative diseases of the nervous system, and lymphoproliferative diseases are among the most important unmanageable diseases of man. Herpesviruses are known to be responsible for certain of these diseases, and are among the likely candidates as etiologic agents for others, including multiple sclerosis. To further understand those diseases, we propose to define the pathogenesis of infection for 2 model systems in which herpesviruses induce nervous system and lymphoproliferative disease. In one, a mouse-herpes simple virus system, mice with acute nervous system disease later recover from paralysis. The virologic and morphologic aspects of acute disease are currently being defined. In the future, recovered animals will be subjected to various physiologic and immunologic manipulations designed to precipitate recurrent and chronic disease. Pathologic consequences of these manipulations will be systematically studied with quantitative virologic and morphologic techniques. In the other disease, Marek's disease of the domestic chicken, lympho-proliferative disease is associated with degenerative lesions in the nervous sytem. The pathogenesis of this disease will be studied in quantitative in vitro systems consisting of explanted organized nervous tissue and lymphocytes.